The purpose of the proposed research is to develop and compare the complete primary structures of bovine and human prothrombin. The approach to this task will be made in terms of developing the sequence of each activation intermediate of the prothrombin molecule using the automated Edman technique. Initial studies will be conducted with each intact intermediate. Later studies will be directed at the sequence of chemically or enzymatically derived fragments of prothrombin and its intermediates. Studies have been extended to examine the differences between the human, canine and bovine activation mechanisms, and the locations of the gamma carboxy glutamic acid residues in the structure. At this point a completely documented structure has been completed for human prothrombin 1. In addition, we wish to identify the structural defect in a recently discovered congenitally abnormal prothrombin -"Prothrombin Quick". This protein is defective in the thrombin portion of the molecule.